2003/07/18 by Christian Andriamampandry, Omar Taleb, Sandrine Viry +5 · 2 citations
Neuroscience · Pharmacology, Toxicology and Pharmaceutics · #Neuroscience and Neuropharmacology Research #Neurotransmitter Receptor Influence on Behavior #Forensic Toxicology and Drug Analysis
paper · doi:10.1096/fj.02-0846fje
openalex publication_date 2003/07/18 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/23
Gamma-hydroxybutyrate (GHB) is an endogenous neuromodulator with therapeutical applications in anesthesia, sleep disorders, and drug addiction. We report the cloning of a GHB receptor from a rat hippocampal cDNA library. This receptor has a molecular mass of 56 kDa and belongs to the seven-transmembrane receptor family. The peptidic sequence has no significant homology with any known receptor, including GABA(B) receptors. Its mRNA is restricted to the brain and is particularly abundant in the hippocampus, cortex, striatum, thalamus, olfactory bulbs, and cerebellum, matching the distribution of GHB binding sites in rat brain. Southern blot revealed the presence of homologous sequences in several species including the human. Binding assays on transfected CHO cells showed a dissociation constant (Kd) of 426 nM for GHB and no affinity for GABA, baclofen, or glutamate. In patch-clamp experiments, transfected CHO cells revealed a functional G-protein-coupled receptor as demonstrated by GTP-gamma-S-induced irreversible activation. Application of 0.1-15 microM GHB specifically induced an inward current at negative membrane potentials that was not reproduced by application of baclofen (10 microM). CGP-55845, a GABA(B) receptor antagonist, did not inhibit the GHB-induced response nor did the GHB receptor antagonist NCS-382, suggesting that the GHB receptor system includes several subtypes.